The use of microphysiological systems to model metastatic cancer.

Cancer is one of the leading causes of death in the 21st century, with metastasis of cancer attributing to 90% of cancer-related deaths. Therefore, to improve patient outcomes there is a need for better preclinical models to increase the success of translating oncological therapies into the clinic. Current traditional staticmodels lack a perfusable network which is critical to overcome the diffusional mass transfer limit to provide a mechanism for the exchange of essential nutrients and waste removal, and increase their physiological relevance.

Gelatin-containing porous polycaprolactone PolyHIPEs as substrates for 3D breast cancer cell culture and vascular infiltration.

Tumour survival and growth are reliant on angiogenesis, the formation of new blood vessels, to facilitate nutrient and waste exchange and, importantly, provide a route for metastasis from a primary to a secondary site. Whilst current models can ensure the transport and exchange of nutrients and waste via diffusion over distances greater than 200 μm, many lack sufficient vasculature capable of recapitulating the tumour microenvironment and, thus, metastasis. In this study, we utilise gelatin-containing polymerised high internal phase emulsion (polyHIPE) templated polycaprolactone-methacrylate (PCL-M) scaffolds to fabricate a composite material to support the 3D culture of MDA-MB-231 breast cancer cells and vascular ingrowth.

Surfactant-free gelatin-stabilised biodegradable polymerised high internal phase emulsions with macroporous structures.

High internal phase emulsion (HIPE) templating is a well-established method for the generation of polymeric materials with high porosity (>74%) and degree of interconnectivity. The porosity and pore size can be altered by adjusting parameters during emulsification, which affects the properties of the resulting porous structure. However, there remain challenges for the fabrication of polyHIPEs, including typically small pore sizes (∼20-50 μm) and the use of surfactants, which can limit their use in biological applications.

Development of PCL PolyHIPE Substrates for 3D Breast Cancer Cell Culture.

Cancer is a becoming a huge social and economic burden on society, becoming one of the most significant barriers to life expectancy in the 21st century. In particular, breast cancer is one of the leading causes of death for women. One of the most significant difficulties to finding efficient therapies for specific cancers, such as breast cancer, is the efficiency and ease of drug development and testing.

A systematic review of literature on occupational health and safety interventions for older workers.

As the global population ages there is an imperative to enhance labour participation of older workers in ways that support good physical and psychological health. However, there is limited guidance for organisations on how to do this effectively. This systematic review examined literature identified through four databases and a targeted web-search, yielding 39 PRISMA records (32 scholarly, seven grey literature) reporting workplace interventions aimed at improving the injury outcomes of older workers.

Elastomeric, bioadhesive and pH-responsive amphiphilic copolymers based on direct crosslinking of poly(glycerol sebacate)--polyethylene glycol.

Poly(glycerol sebacate) (PGS), a synthetic biorubber, is characterised by its biocompatibility, high elasticity and tunable mechanical properties; however, its inherent hydrophobicity and insolubility in water make it unsuitable for use in advanced biomaterials like hydrogels fabrication. Here, we developed new hydrophilic PGS-based copolymers that enable hydrogel formation through use of two different types of polyethylene glycol (PEG), polyethylene glycol (PEG2) or glycerol ethoxylate (PEG3), combined at different ratios. A two-step polycondensation reaction was used to produce poly(glycerol sebacate)--polyethylene glycol (PGS--PEG) copolymers that were then crosslinked thermally without the use of initiators or crosslinkers, resulting in PGS--PEG2 and PGS--PEG3 amphiphilic polymers.

Porous biomaterials for tissue engineering: a review.

The field of biomaterials has grown rapidly over the past decades. Within this field, porous biomaterials have played a remarkable role in: (i) enabling the manufacture of complex three-dimensional structures; (ii) recreating mechanical properties close to those of the host tissues; (iii) facilitating interconnected structures for the transport of macromolecules and cells; and (iv) behaving as biocompatible inserts, tailored to either interact or not with the host body. This review outlines a brief history of the development of biomaterials, before discussing current materials proposed for use as porous biomaterials and exploring the state-of-the-art in their manufacture.

Production of a high purity, C-tagged hepatitis B surface antigen fusion protein VLP vaccine for malaria expressed in Pichia pastoris under cGMP conditions.

Virus-like particles (VLPs) induce strong humoral and cellular responses and have formed the basis of some currently licensed vaccines. Here, we present the method used for the production of R21, a VLP-based anti-sporozoite malaria vaccine, under current Clinical Good Manufacturing Practice regulations (cGMP). Previous preclinical studies in BALB/c mice showed that R21 produced almost complete protection against sporozoite challenge with transgenic Plasmodium berghei parasites.

Corrected and Republished from: "A Novel, Multiple-Antigen Pneumococcal Vaccine Protects against Lethal Challenge".

Current vaccination against Streptococcus pneumoniae uses vaccines based on capsular polysaccharides from selected serotypes and has led to nonvaccine serotype replacement disease. We have investigated an alternative serotype-independent approach, using multiple-antigen vaccines (MAV) prepared from S. pneumoniae TIGR4 lysates enriched for surface proteins by a chromatography step after culture under conditions that induce expression of heat shock proteins (Hsp; thought to be immune adjuvants).

The Importance of Mimicking Dermal-Epidermal Junction for Skin Tissue Engineering: A Review.

There is a distinct boundary between the dermis and epidermis in the human skin called the basement membrane, a dense collagen network that creates undulations of the dermal-epidermal junction (DEJ). The DEJ plays multiple roles in skin homeostasis and function, namely, enhancing the adhesion and physical interlock of the layers, creating niches for epidermal stem cells, regulating the cellular microenvironment, and providing a physical boundary layer between fibroblasts and keratinocytes. However, the primary role of the DEJ has been determined as skin integrity; there are still aspects of it that are poorly investigated.

Electrospun Fiber Alignment Guides Osteogenesis and Matrix Organization Differentially in Two Different Osteogenic Cell Types.

Biomimetic replication of the structural anisotropy of musculoskeletal tissues is important to restore proper tissue mechanics and function. Physical cues from the local micro-environment, such as matrix fiber orientation, may influence the differentiation and extracellular matrix (ECM) organization of osteogenic progenitor cells. This study investigates how scaffold fiber orientation affects the behavior of mature and progenitor osteogenic cells, the influence on secreted mineralized-collagenous matrix organization, and the resulting construct mechanical properties.

Low-Fluence Photodynamic Therapy Parameter Screening Using 3D Tumor Spheroids Shows that Fractionated Light Treatments Enhance Phototoxicity.

The evaluation of novel photosensitizers (PSs) for photodynamic therapy (PDT) is difficult due to the limitations of two-dimensional cell culture and multiple parameters (dose, light intensity, uptake time), which complicate progression to experiments and clinical translation. Three-dimensional (3D) cell culture models like multicellular cancer tumor spheroids (MCTS) show great similarities to avascular tumor conditions, improving the speed and accuracy of screening novel compounds with various treatment combinations. In this study, we utilize C8161 human melanoma spheroids to screen PDT treatment combinations using protoporphyrin IX (PpIX) and drug-loaded carbon dot (CD) conjugates PpIX-CD and PpIX@CD at ultralow fluence values (<10 J/cm).

Understanding Surface Modifications Induced via Argon Plasma Treatment through Secondary Electron Hyperspectral Imaging.

Understanding the effects that sterilization methods have on the surface of a biomaterial is a prerequisite for clinical deployment. Sterilization causes alterations in a material's surface chemistry and surface structures that can result in significant changes to its cellular response. Here we compare surfaces resulting from the application of the industry standard autoclave sterilisation to that of surfaces resulting from the use of low-pressure Argon glow discharge within a novel gas permeable packaging method in order to explore a potential new biomaterial sterilisation method.

State of science: the future of work - ergonomics and human factors contributions to the field.

This article is concerned with scholarly ergonomics and human factors (E/HF) contributions to date to the field of research inquiry known as the 'future of work'. The review considers E/HF perspectives on how the nature of work is changing and what this means for the practice of E/HF and for human performance and wellbeing at work. This field of research has attracted much attention from scholars from various disciplines as flexible working arrangements and casualised employment, in particular, have come under the microscope during the COVID-19 pandemic.

Mitochondriotropic lanthanide nanorods: implications for multimodal imaging.

Two-photon active mitochondriotropic lanthanide nanorods for high resolution fluorescence imaging. The presence of Gd in the nanorods also enabled us to utilize this material as a T-T dual-mode contrast reagent for recording magnetic resonance images of the mouse brain.

Characterizing Cross-Linking Within Polymeric Biomaterials in the SEM by Secondary Electron Hyperspectral Imaging.

A novel capability built upon secondary electron (SE) spectroscopy provides an enhanced cross-linking characterization toolset for polymeric biomaterials, with cross-linking density and variation captured at a multiscale level. The potential of SE spectroscopy for material characterization has been investigated since 1947. The absence of suitable instrumentation and signal processing proved insurmountable barriers to applying SE spectroscopy to biomaterials, and consequently, capturing SE spectra containing cross-linking information is a new concept.

Porous microspheres support mesenchymal progenitor cell ingrowth and stimulate angiogenesis.

Porous microspheres have the potential for use as injectable bone fillers to obviate the need for open surgery. Successful bone fillers must be able to support vascularisation since tissue engineering scaffolds often cease functioning soon after implantation due to a failure to vascularise rapidly. Here, we test the angiogenic potential of a tissue engineered bone filler based on a photocurable acrylate-based high internal phase emulsion (HIPE).

Adenovirus 5 recovery using nanofiber ion-exchange adsorbents.

Viral vectors such as adenovirus have successful applications in vaccines and gene therapy but the manufacture of the high-quality virus remains a challenge. It is desirable to use the adsorption-based chromatographic separations that so effectively underpin the therapeutic protein manufacture. However fundamental differences in the size and stability of this class of product mean it is necessary to revisit the design of sorbent's morphology and surface chemistry.

Two photon excitable graphene quantum dots for structured illumination microscopy and imaging applications: lysosome specificity and tissue-dependent imaging.

Biocompatible graphene quantum dots (GQDs), obtained from extracts of neem root, are found to be suitable for structured illumination microscopy and two-photon microscopy (TPM). Results of TPM and confocal luminescence microscopy ensure lysosome specificity in live cells and tissue-dependent localization in zebrafish, respectively, of GQDs.

A Novel, Multiple-Antigen Pneumococcal Vaccine Protects against Lethal Challenge.

Current vaccination against uses vaccines based on capsular polysaccharides from selected serotypes and has led to nonvaccine serotype replacement disease. We have investigated an alternative serotype-independent approach, using multiple-antigen vaccines (MAV) prepared from TIGR4 lysates enriched for surface proteins by a chromatography step after culture under conditions that induce expression of heat shock proteins (Hsp; thought to be immune adjuvants). Proteomics and immunoblot analyses demonstrated that, compared to standard bacterial lysates, MAV was enriched with Hsps and contained several recognized protective protein antigens, including pneumococcal surface protein A (PspA) and pneumolysin (Ply).

Imaging cellular trafficking processes in real time using lysosome targeted up-conversion nanoparticles.

β-NaYF:Yb,Gd up-conversion nanoparticles, UCNPs, surface functionalized with suitable targetting peptides function as nontoxic lysosome-specific imaging probes.

A new mode of contrast in biological second harmonic generation microscopy.

Enhanced image contrast in biological second harmonic imaging microscopy (SHIM) has previously been reported via quantitative assessments of forward- to epi-generated signal intensity ratio and by polarization analysis. Here we demonstrate a new form of contrast: the material-specific, wavelength-dependence of epi-generated second harmonic generation (SHG) excitation efficiency, and discriminate collagen and myosin by ratiometric epi-generated SHG images at 920 nm and 860 nm. Collagen shows increased SHG intensity at 920 nm, while little difference is detected between the two for myosin; allowing SHIM to characterize different SHG-generating components within a complex biological sample.